Neurons synthesize a greater variety of K+ channel types that are fundamental components in the control of neuronal activity. This proposal is aimed at determining the fundamental cellular mechanisms that regulate the diversity of voltage-dependent K+ channels. We have exciting and interesting new finding that beta-subunit polypeptide isoforms exhibit differential selectivity among highly related K+ channel alpha-subunit polypeptides, both in rat brain and in transfected mammalian cells. We propose to determine the molecular basis for the selective interaction of K+ channel alpha- and beta-subunit polypeptides, and the biochemical consequences of these interactions on K+ channel protein complex. That K+ channel beta-subunits are present in complexes with only a defined subset of alpha-subunits in rat brain, shows that precise molecular mechanisms exist to regulae alpha/beta subunit interaction. Thus, the determination of the subunit composition of neuronal K+ channels, and the molecular mechanisms controlling the selective interaction of alpha- and beta-subunit polypeptides, are important aspects of understanding the regulation of K+ channel expression in the mammalian central nervous system. It is certain that the differential assembly of subunits is a major mechanism to generate diversity of K+ channels in the mammalian central nervous system. It is also clear that the subunit composition of brain K+ channel complexes determines to a great extent their functional properties and subcellular distribution. As regulation of K+ channel activity influences action potential duration, amplitude and frequency, and synaptic efficacy, understanding the mechanisms controlling the composition of k+ channel complexes at the molecular level, anticipated from our proposed studies, will provide insights into the normal and abnormal function of neurons. It will thus contribute to the eventual understanding and treating of a variety of neurological disorders, including genetic and acquired epilepsy, cognitive disorders, and affective disorders.